Stem/progenitor cell transplantation has emerged as a potential therapeutic modality for numerous conditions. For cardiac applications, cell injections have usually been accomplished under direct control through multiple epicardial punctures. However, to reduce the invasiveness of the procedure, percutaneous approaches are undergoing development. In the setting of these percutaneous techniques, the transvenous approach, using a specifically dedicated coronary sinus catheter, is particularly attractive because of its greater simplicity compared with the endoventricular route. Initial studies have established the effectiveness of bone marrow stem cell (BMC) transvenous transfer into the myocardium (Thomson et al., J. Am. Coll. Cardiol., 34:7514 (2002)). Intracoronary injections of bone marrow mononuclear cells concomitant with angioplasty at the acute stage of myocardial infarction (MI) have also shown promising results (Strauer et al., Circ., 106:1913 (2002); Assmus et al., Circ., 106:3009 (2002)).
More recent efficacy data from preliminary studies in which patients with an acute MI were treated by application of BMC showed a 7-9% improvement in global LV ejection fraction, as well as improvements in regional wall motion, perfusion, and LV end systolic volumes four to six months after intracoronary BMC transplantation (see Wollert et al., Circ. Res., 96:151 (2005); Haider et al., Am. J. Physiol. Circ. Physiol., 288:H2557 (2005); Dimmeler et al., J. Clin. Investig., 115:572 (2005)). In particular, the final one-year results of the TOPCARE-AMI trial, demonstrated a sustained improvement of LV function, reduced infarct size, and an absence of reactive hypertrophy after intracoronary BMC transplantation, suggesting functional regeneration of the infarcted ventricles and a prevention of remodeling (Schachinger et al., J. Am. Coll. Cardiol., 44:1690 (2004)). These findings are despite the observation that only 1.3-2.6% of the transplanted BMC are ultimately retained in the infarct after intracoronary transfer (Hofmann et al., Circ., 111:2198 (2005)).
However, most transplanted cells never initially engraft (Christman et al., J. Am. Coll. Cardiol., 44:465 (2004)), very few are viable within one week post injection (Gojo et al., Exp. Cell. Res., 288:51 (2003)), and the vast majority of transplanted cells die (Minami et al., J. Am. Coll. Cardiol., 41:1084 (2003)). Thus, regardless of the route of delivery, cell number and cell death remain major limitations of cell transplantation. For instance, it is uncertain whether multiplication of those that have survived can replace the high attrition rate.
What is needed is an improved method to enhance homing, engraftment and retention of transplanted therapeutic cells.